Imiquimod 3.75% cream applied daily to treat anogenital warts: combined results from women in two randomized, placebo-controlled studies

David A Baker, Daron G Ferris, Mark G Martens, Kenneth H Fife, Stephen K Tyring, Libby Edwards, Anita Nelson, Kevin Ault, Kenneth F Trofatter, Tiepu Liu, Sharon Levy, Jason Wu, David A Baker, Daron G Ferris, Mark G Martens, Kenneth H Fife, Stephen K Tyring, Libby Edwards, Anita Nelson, Kevin Ault, Kenneth F Trofatter, Tiepu Liu, Sharon Levy, Jason Wu

Abstract

Objective: To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts.

Methods: In two studies 534 women ≥12 years of age (mean 33.4) with 2-30 warts (mean 7.9) and total wart area ≥10 mm(2) (mean 166.3) were randomized (1:2:2) to placebo (106), imiquimod 2.5% (212) or 3.75% (216) creams applied once daily until complete clearance or a maximum of 8 weeks.

Results: For placebo, imiquimod 2.5% and 3.75%, respectively, complete clearance of all warts was achieved in 14.2%, 28.3%, and 36.6% of women (intent-to-treat, P = 0.008 imiquimod 2.5%, and P < 0.001 3.75% versus placebo). Mean changes in wart counts were -10.7%, -50.9%, and -63.5% (per-protocol, P < 0.001 each active versus placebo) and safety-related discontinuation rates 0.9%, 1.4%, and 2.3%.

Conclusions: Imiquimod 3.75% applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts.

Figures

Figure 1
Figure 1
Disposition of women in the studies, combined, evaluation phase. Percents displayed are percent of women randomized by treatment group. Adverse events category includes women discontinuing for local skin reactions.
Figure 2
Figure 2
Complete clearance rates. (a) Intent to treat (b) per protocol. White: placebo, stippled: imiquimod 2.5%, solid black: imiquimod 3.75%. P-values from a Cochran-Mantel-Haenszel test, stratified by analysis site using two treatment groups at a time.*indicates statistically significant for active versus placebo, and †for imiquimod 3.75% versus 2.5%, using Hochberg's modified Bonferroni procedure. Bars indicate 95% confidence interval calculated using exact method.
Figure 3
Figure 3
Partial clearance rates and change in wart count from baseline. White: placebo, stippled: imiquimod 2.5%, solid black: imiquimod 3.75%. (a) Partial (≥75% reduction in wart count compared to baseline) clearance rates, PP. P values from a Cochran-Mantel-Haenszel test, stratified by analysis site using two treatment groups at a time.*indicates statistically significant for active versus placebo, and †for imiquimod 3.75% versus 2.5%, using Hochberg's modified Bonferroni procedure. Bars indicate 95% confidence interval calculated using exact method. (b) Change in wart count compared with baseline, mean percent, PP. P values from an analysis of covariance test, controlling for baseline wart count and analysis site.*indicates statistically significant for active versus placebo, and †for imiquimod 3.75% versus 2.5%, using Hochberg's modified Bonferroni procedure.
Figure 4
Figure 4
Change in wart count compared with baseline (left axis, circle, mean, ITT, last observation carried forward) versus local skin reaction (LSR) sum score (right axis, square, mean, observed) over time for imiquimod 3.75% during the evaluation phase. Maximum LSR sum score = 18. Shaded box indicates treatment period of up to 8 weeks. P values were calculated using analysis of covariance, controlling for baseline wart count, and analysis site.*indicates statistically significant for active versus placebo, and †for imiquimod 3.75% versus 2.5%, using Hochberg's modified Bonferroni procedure.

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